Laboratory of Proteins Engineering and Bioactive Molecules (LIP-MB), National Institute of Applied Sciences and Technology of Tunis (INSAT), The University of Carthage, Tunis, Tunisia.
Department of Research, Advanced Diagnostics and Technological Innovation, UOSD SAFU Unit-Translational Research Area, IRCCS, Regina Elena National Cancer Institute, Rome, Italy.
Mol Biol Rep. 2019 Oct;46(5):4743-4750. doi: 10.1007/s11033-019-04920-6. Epub 2019 Jun 18.
There is a major need for the identification of biomarkers, which are able to guide personalized therapy for bladder cancer, in particular after resection of the primary tumor. Specifically, miR-9 upregulation has been preliminarily associated with a more aggressive phenotype of bladder cancer, namely muscle-invasive bladder cancer (MIBC) or high-grade non-muscle-invasive bladder cancer (HG NMIBC). In order to explore the potential utility of miR-9 as a biomarker in bladder cancer, we have investigated its expression pattern in a sample of Tunisian patients who have undergone primary resection. This is a retrospective study performed on BCa samples from 90 patients (44 specimens of HG NMIBC, 23 specimens of LG NMIBC, and 23 specimens of MIBC). Ten samples from the non-tumoral zone of cystectomy specimens were used as controls. For each specimen, we measured miR-9 expression and correlated it with the clinical characteristics of the patients. Overall, miR-9 was overexpressed in MIBC compared to NMIBC specimens (median fold change [FC]: - 8.89 vs 1.41, p = 0.001). Similarly, miR-9 expression was significantly different in LG NMIBC, HG NMIBC and MIBC subgroups (median FC: 0.68, 2.14 and 8.89, respectively; p = 0.001). ROC analysis showed that miR-9 expression pattern could be used as potential biomarker for distinguishing NMIBC subgroups: indeed miR-9 expression is relatively low in LG NMIBC and high in HG NMIBC. The thresholds are estimated at 0.063 and 21.597, respectively. Moreover, miR-9 was associated with a higher risk of progression. This study suggests the clinical value of miR-9 as a prognostic factor in bladder cancer after tumor resection. Should the prognostic ability of miR-9 be confirmed in larger studies, also on different ethnic groups, it would be useful to investigate whether urine sampling-which is easier to perform, less invasive and less costly-can provide the same results as analysis on surgical specimens.
目前非常需要鉴定生物标志物，以便为膀胱癌患者，特别是在原发性肿瘤切除后，提供个性化治疗指导。具体而言，miR-9 的上调与膀胱癌侵袭性更强的表型有关，即肌层浸润性膀胱癌（MIBC）或高级别非肌层浸润性膀胱癌（HG NMIBC）。为了探讨 miR-9 作为膀胱癌生物标志物的潜在效用，我们研究了其在接受初次切除术的一组突尼斯患者样本中的表达模式。这是一项回顾性研究，涉及 90 名患者的 BCa 样本（44 份 HG NMIBC 标本、23 份 LG NMIBC 标本和 23 份 MIBC 标本）。从膀胱切除术标本的非肿瘤区采集 10 份样本作为对照。我们测量了每个标本中的 miR-9 表达水平，并将其与患者的临床特征相关联。总的来说，MIBC 样本中的 miR-9 表达水平高于 NMIBC 样本（中位数倍数变化[FC]：-8.89 对 1.41，p=0.001）。同样，LG NMIBC、HG NMIBC 和 MIBC 亚组中 miR-9 的表达差异也具有统计学意义（中位数 FC：0.68、2.14 和 8.89，p=0.001）。ROC 分析表明，miR-9 的表达模式可用作区分 NMIBC 亚组的潜在生物标志物：实际上，LG NMIBC 中的 miR-9 表达水平较低，而 HG NMIBC 中的 miR-9 表达水平较高。相应的阈值估计值分别为 0.063 和 21.597。此外，miR-9 与进展风险较高相关。本研究表明，miR-9 作为肿瘤切除后膀胱癌的预后因素具有临床价值。如果 miR-9 的预后能力在更大规模的研究中得到证实，并且也在不同的种族群体中得到证实，那么研究尿液取样（其更容易实施、侵袭性更小且成本更低）是否可以提供与手术标本分析相同的结果将是有用的。
